TCM syndrome differentiation in colorectal cancer patients assisted by differences in gut microbiota: An exploratory study

OBJECTIVE: To explore the difference in gut microbiota between different traditional Chinese Medicine (TCM) syndromes in patients with colorectal cancer (CRC) and its internal relationship. METHODS: From June 2020 to August 2021, 109 colorectal cancer patients with a clear pathological diagnosis who had not yet undergone surgery or chemotherapy were classified according to the TCM syndrome classification, and the feces samples of 109 patients with preoperative colorectal cancer were collected. 16s rRNA gene sequencing was used to determine gut microbiota diversity and abundance in CRC patients with different TCM syndrome, and LEfSe analysis was made to screen different TCM syndrome for differential representative microbiota. RESULTS: 109 patients were divided into 5 syndromes by TCM syndrome classification, which were Liver and Kidney Yin Deficiency Syndrome (LKYDS, n = 19), Spleen Deficient Qi Stagnation Syndrome (SDQSS, n = 30), Stasis and Poison Obstruction Syndrome (SPOS, n = 17), Damp-Heat Syndrome (DHS, n = 30), Qi and Blood Deficiency Syndrome (QBDS, n = 13). Alpha diversity index showed significant differences among the five groups of TCM syndromes, with Shannon index being highest in the SDQSS group and lowest in the LKYDS (p = 0.003). ACE index being highest in the SDQSS group and lowest in the SPOS (p = 0.010). PD whole tree index being highest in the SDQSS group and lowest in the SPOS (p = 0.017). Similarly, beta diversity showed significant differences among the five groups of TCM syndromes, with principal coordinate analysis (PCo1 = 31.86 %, PCo2 = 5.62 %) showing separation and coincidence between the groups, and Adonis group differences showing coincidence between the QBDS-LKYDS (p = 0.702), QBDS-DHS (p = 0.133), and SDQSS-DHS (p = 0.260) groups. LEfSe analysis revealed that the representative microbiota of DHS patients was Dialister sp Marseille P5638 (LDA = 3.05, p＜0.001), the representative microbiota of SPOS patients was Oscillospirales (LDA = 4.78, p = 0.029), the representative microbiota of SDQSS patients was Selenomonadaceae (LDA = 3.94, p = 0.003), the representative microbiota of LKYDS patients was Dialister (LDA = 4.19, p = 0.001), and the representative microbiota of QBDS patients was Akkermansia muciniphila (LDA = 4.23, p = 0.006). CONCLUSIONS: There are significant differences in gut microbiota between different TCM syndromes in CRC patients. The five microbiota, Dialister sp Marseille P5638, Oscillospirales, Selenomonadaceae, Dialister, and Akkermansia muciniphila, may be differential markers of TCM syndrome in CRC and are expected to be one of the bases for accurate TCM syndrome differentiation of CRC.